Structure and Function of the Boundaries of Imprinted Genome Domains

哺乳动物的印迹基因聚集在基因组的特定区域，形成“印迹基因组域”。然而，我们不知道每个印迹域是如何定义或划分的。我们研究了7号染色体远端大印迹结构域的着丝粒边界（H19-L23mrp基因间区）的结构和功能，得到了以下结果：1。在基因间区发现了一个没有大ORF的非印迹转录本（Nctc 1）。2. 人类和小鼠之间的序列比较揭示了10个进化上保守的片段，其中7个在转基因小鼠中作为组织特异性增强子起作用。3. 由于L23mrp在体内不利用增强子，我们将L23mrp转基因与增强子连接，并检测增强子是否能在转基因小鼠中激活L23mrp启动子。然而，启动子本身的活性太高，无法评估增强子对启动子的影响。4. 非编码转录本的存在和增强子的聚集组织类似于珠蛋白位点的位点控制区（LCR）。由于已知珠蛋白LCR含有边界元件或绝缘体，因此可能在该边界区域中有类似的机制起作用。

Imprinted genes of mammals are clustered at certain regions of the genome and forms "imprinted genome domains". However, it is unknown how each imprinted domain is defined or delimited. We investigated the structure and function of the centromeric boundary (H19-L23mrp intergenic region) of the large imprinted domain on distal chromosome 7, and obtained the following results. 1 . A non-imprinted transcripts with no large ORF (Nctc 1) was identified in the intergenic region. 2. A sequence comparison between human and mouse revealed ten evolutionarily conserved segments, and seven of these worked as tissue-specific enhancers in transgenic mice. 3. Since L23mrp does not utilize the enhancers in vivo, we linked an L23mrp transgene to the enhancers and examined whether the enhancers can activate the L23mrp promoter in transgenic mice. However, the activity of the promoter itself was too high to assess the effect of the enhancers on the promoter. 4. The presence of non-coding transcripts and the clustered organization of the enhancers resembled the locus control region (LCR) of the globin locus. Since the globin LCR is known to contain a boundary element or an insulator, it is possible that a similar mechanism operates in this boundary region.